BACKGROUND: Postoperative delirium is an important public health concern without effective prevention strategies. This study tested the hypothesis that perioperative epidural use would be associated with decreased risk of delirium through postoperative day 3. METHODS: This was a secondary, observational, nonrandomized analysis of data from The Prevention of Delirium and Complications Associated With Surgical Treatments Trial (PODCAST; NCT01690988). The primary outcome of the current study was the incidence of delirium (ie, any positive delirium screen, postanesthesia care unit through postoperative day 3) in surgical patients (gastrointestinal, hepatobiliary-pancreatic, gynecologic, and urologic) receiving postoperative epidural analgesia compared to those without an epidural. As a secondary outcome, all delirium assessments were then longitudinally analyzed in relation to epidural use throughout the follow-up period. Given the potential relevance to delirium, postoperative pain, opioid consumption, sleep disturbances, and symptoms of depression were also analyzed as secondary outcomes. A semiparsimonious multivariable logistic regression model was used to test the association between postoperative epidural use and delirium incidence, and generalized estimating equations were used to test associations with secondary outcomes described. Models included relevant covariates to adjust for confounding. RESULTS: In total, 263 patients were included for analysis. Epidural use was not independently associated with reduced delirium incidence (adjusted odds ratio, 0.65 [95% CI, 0.32–1.35]; P= .247). However, when analyzing all assessments over the follow-up period, epidural patients were 64% less likely to experience an episode of delirium (adjusted odds ratio, 0.36 [95% CI, 0.17–0.78]; P= .009). Adjusted pain scores (visual analog scale, 0–100 mm) were significantly lower in the epidural group on postoperative day 1 (morning, −16 [95% CI, −26 to −7], P
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